title: Irbesartan treatment does not influence plasma levels of the advanced glycation end products N(epsilon)(1-carboxymethyl)lysine and N(epsilon)(1-carboxyethyl)lysine in patients with type 2 diabetes and microalbuminuria. A randomized controlled trial.
abstract: BACKGROUND
  In vitro and animal experiments have shown inhibiting effects of angiotensin receptor blockers (ARBs) on the formation of advanced glycation end products (AGEs), which are known to be involved in the development of cardiovascular complications in diabetes. However, sufficient human data to confirm such beneficial effects of ARBs on AGEs are lacking. Therefore, we investigated the effects of irbesartan treatment on plasma levels of the AGEs N(ε)(1-carboxymethyl)lysine (CML) and N(ε)(1-carboxyethyl)lysine (CEL) in hypertensive patients with type 2 diabetes and microalbuminuria.
  
  
  METHODS
  We analysed data from a multicentre, double-blind, parallel, randomized controlled trial in patients with type 2 diabetes and microalbuminuria, the primary goal of which was to examine the renoprotective effects of irbesartan treatment (150 or 300 mg daily). Secondary end points included plasma CML and CEL in the treatment arm receiving 300 mg irbesartan (n = 139) and in the placebo group (n = 125). Effects of treatment at 1- and 2-year follow-up were analysed by means of generalized estimating equations according to an intention-to-treat principle.
  
  
  RESULTS
  Levels of CML and CEL did not differ between groups at baseline. No significant changes were observed in CML and CEL over time in either group and there was no effect of treatment on CML and CEL at any time-point. Mean differences for the irbesartan versus placebo group over time were -0.96 μmol/mol lysine (95% confidence interval: -3.43 to 1.51) for CML and -0.10 μmol/mol lysine (-0.76 to 0.56) for CEL.
  
  
  CONCLUSIONS
  Long-term irbesartan treatment does not influence plasma levels of the AGE CML and CEL in patients with type 2 diabetes and microalbuminuria.
authors.affiliation: Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Lian
authors.initials: L
authors.lastname: Engelen
authors.forename: Frederik
authors.initials: F
authors.lastname: Persson
authors.forename: Isabel
authors.initials: I
authors.lastname: Ferreira
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
authors.forename: Peter
authors.initials: P
authors.lastname: Hovind
authors.forename: Tom
authors.initials: T
authors.lastname: Teerlink
authors.forename: Coen D
authors.initials: CD
authors.lastname: Stehouwer
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D048909:Diabetes Complications / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D000077405:Irbesartan; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D057911:Angiotensin Receptor Antagonists; D015415:Biomarkers; D001713:Biphenyl Compounds; D017127:Glycation End Products, Advanced; D013777:Tetrazoles; C054688:N(6)-(1-carboxyethyl)lysine; C048496:N(6)-carboxymethyllysine; D000077405:Irbesartan; D008239:Lysine